Normal Menstruation and the Menstrual Cycle

Question 1

what defines the length of the menstrual cycle?

Answer 1

days between first day of bleeding > onset of bleeding in the next cycle

Question 2

normal length of cycle?

Answer 2

21-35 days

usually 28 days

Question 3

when is menstrual cycle usually most irregular?

Answer 3

around extremes of reproductive life due to anovulation and inadequate follicular development

Question 4

length of follicular and luteal phase?

Answer 4

luteal phase = always 14 days

follicular phase = can vary from 10-16 days

Question 5

what type of hormone is GnRH?

Answer 5

peptide

released from hypothalamus

Question 6

how is GnRH released?

Answer 6

in a pulsatile manner

Question 7

briefly describe HPO axis?

Answer 7

hypothalamus releases GnRH > anterior pituitary releases FSH and LH
- FSH acts on granulosa cells which secrete oestrogen and inhibin
- LH acts on theca cells which secrete androgens (androgens are converted to oestrogens by aromatase)
inhibin acts as negative feedback on anterior pituitary to reduce FSH production
oestrogen provides negative feedback to anterior pituitary and hypothalamus

Question 8

how does oestrogen provide negative feedback?

Answer 8

mod oestrogen levels = negative feedback on HPO axis
high oestrogen levels (in absence of progesterone) = positive feedback on HPO axis
oestrogen in presence of progesterone = negative feedback on HPO axis

Question 9

what are the 3 events in the ovarian cycle?

Answer 9

follicular phase
ovulation
luteal phase

Question 10

follicular phase summary?

Answer 10

FSH rises in first few days > follicle grows in ovary > oestrogen produced by granulosa cells and via conversion of androgens from theca cells > oestrogen and inhibin act as negative feedback and decrease FSH release from pituitary > results in follicle with most FSH receptors (dominant follicle) getting most of the little FSH and continuing development while others degrade > dominant follicle continues producing oestrogen and inhibin which enhances androgen synthesis under LH control

Question 11

what other hormones play a role in follicular phase?

Answer 11

inhibin and activin

IGF-1, IGF-2

Question 12

what does inhibin do in females?

Answer 12

…produced by granulosa cells and feeds back to pituitary to downregulate FSH release
also enhances androgen release

Question 13

what does activin do in females?

Answer 13

also produced by granulosa cells and pituitary
opposite to inhibin
works to increase FSH release

Question 14

when does ovulation begin?

Answer 14

when the dominant follicle has fully grown and matured during follicular phase (average = 14 days)

Question 15

what happens in ovulation?

Answer 15

lower FSH levels (due to negative feedback) forces LH receptors on the granulosa cells to compensate > oestrogen production increases until threshold where it then exerts positive feedback causing the LH surge > ovulation occurs around 12 hours after LH surge when the dominant follicle ruptures and releases oocyte

Question 16

oestrogen increases up to threshold level during ovulation phase over a period of 24-36 hrs, what else happens during this time?

Answer 16

the LH-induced lutenization of granulosa cells causes progesterone to be produced
this progesterone adds to the positive feedback for LH secretion and causes a small periovulatory rise in FSH as well

Question 17

what happens in the luteal phase?

Answer 17

remaining granulosa and theca cells in follicle after rupture and release of oocyte form the corpus luteum > corpus luteum secretes progesterone (beginning of secretory phase of endometrium)
ongoing pituitary LH release acts on lutenized granulosa cells to ensure supply of progesterone which stabilises endometrium for pregnancy > progesterone suppresses FSH and LH secretion to a level that wont cause any more follicle growth in that cycle

Question 18

how does luteal phase progress in absence of pregnancy (no bHCG)?

Answer 18

corpus luteum will undergo luteolysis and regress
this causes decrease in progesterone levels
endometrium is no longer stabilised and therefore sheds causing menstruation
reduced progesterone, oestrogen and inhibin = removal of negative feedback on pituitary therefore FSH etc start to increase again stimulating follicle growth and starting the cycle again

Question 19

when does progesterone peak?

Answer 19

7 days before start of next menses

Question 20

clinical application of progesterone peak?

Answer 20

in assessing infertility and checking for ovulation

mid-luteal phase progesterone can be checked to determine if progesterone at level to cause ovulation?

Question 21

the endometrium is under the influence of what?

Answer 21

sex steroids that circulate in females of reproductive age

Question 22

3 endometrial phases?

Answer 22

proliferative
secretory
menstrual

Question 23

proliferative endometrial phase?

Answer 23

exposure to oestrogen and progesterone results in cellular proliferation and differentiation in preparation for embryo
endometrium changes from a single layer of columnar cells to a pseudostratified epithelium with frequent mitoses

Question 24

what happens in the secretory endometrial phase?

Answer 24

period of endometrial glandular secretory activity
endometrial glands become more torturous, spiral arteries grow and fluid is secreted into glandular cells and into uterine lumen
later, progesterone induces formation of temporary layer (decidua)

Question 25

what is decidualisation?

Answer 25

formation of specialised glandular epithelium (decidua)
irreversible
apoptosis occurs if theres no embryo implantation

Question 26

what happens in menstrual endometrial phase?

Answer 26

day 1
involves shedding of dead endometrium and ceases as endometrium regenerates
oestrogen and progesterone fall around 14 days after ovulation leading to a loss of tissue fluids, vasoconstriction of spiral arteries and distal ischaemia in endometrium
this causes tissue breakdown, loss of upper layer of endometrium (stratum functionalis) along with bleeding from remaining arteries seen as menstruation

Question 27

how is haemostasis in endometrium different to other areas of body?

Answer 27

it does not involve process of clot formation and fibrosis

haemostasis more occurs due to multiple vasoconstrictors and vasodilators (including prostaglandins)

Question 28

good drug to use for heavy menstrual bleeding and why?

Answer 28

NSAIDs such as mefenamic acid

inhibits prostaglandins causing vasoconstriction of spiral arteries

Question 29

how does endoemetrial cycle relate to ovarian cycle?

Answer 29

prolfierative endometrial phase = ovarian follicular phase

secretory endometrial phase = luteal ovarian phase